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pmid:33540700
A Novel Ferroptosis-Associated Gene Signature to Predict Prognosis in Patients with Uveal Melanoma.
Huan Luo · Chao Ma
Diagnostics (Basel, Switzerland) · 2021 doi:10.3390/diagnostics11020219
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Complete file
{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33540700", "kind": "science-record", "revision": 7, "content_hash": "sha256:4157023261099a3e7655e3ff011f3f8e976c29a98b90c5f206578d20828f1f98", "created_at": "2026-11-01T15:41:24Z", "updated_at": "2026-11-01T22:03:02Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "A Novel Ferroptosis-Associated Gene Signature to Predict Prognosis in Patients with Uveal Melanoma.", "doi": "10.3390/diagnostics11020219", "pmid": "33540700", "authors": ["Huan Luo", "Chao Ma"], "journal": "Diagnostics (Basel, Switzerland)", "year": 2021, "abstract": "BACKGROUND: Uveal melanoma (UM) is the most common intraocular tumor in adults. Ferroptosis is a newly recognized process of cell death, which is different from other forms of cell death in terms of morphology, biochemistry and genetics, and has played a vital role in cancer biology. The present research aimed to construct a gene signature from ferroptosis-related genes that have the prognostic capacity of UM.\nMETHODS: UM patients from The Cancer Genome Atlas (TCGA) were taken as the training cohort, and GSE22138 from Gene Expression Omnibus (GEO) was treated as the validation cohort. A total of 103 ferroptosis-related genes were retrieved from the GeneCards. We performed Kaplan-Meier and univariate Cox analysis for preliminary screening of ferroptosis-related genes with potential prognostic capacity in the training cohort. These genes were then applied into an overall survival-based LASSO Cox regression model, constructing a gene signature. The discovered gene signature was then evaluated via Kaplan-Meier (KM), Cox, and ROC analyses in both cohorts. The Pearson correlation coefficient examined the correlations between risk score and UM common mutations and autophagy. The analyses of GSEA and immune infiltrating were performed to better study the functional annotation of the gene signature and the character of each kind of immune cell in the tumor microenvironment.\nRESULTS: A seven-gene signature was found from the training cohort and validated in all cohorts by Kaplan-Meier and Cox regression analyses, revealing its independent prognosis value in UM. Moreover, ROC analysis was conducted, confirming the strong predictive ability that this signature had for UM prognosis. A total of 52.24% (256/490) autophagy-related genes were significantly correlated with risk scores. Analyses of GSEA and immune infiltrating detailed exhibited specific pathways associated with the seven-gene signature, also confirming the crucial role that Mast cells resting played in the prognosis of the seven-gene signature.\nCONCLUSIONS: In this study, a novel ferroptosis-related seven-gene signature (ALOX12, CD44, MAP1LC3C, STEAP3, HMOX1, ITGA6, and AIFM2/FSP1) was built. It could accurately predict UM prognosis and was related to Mast cells resting, which provides the potential for personalized outcome prediction and the development of new therapies in the UM population.", "claims": [{"id": "claim-data-access", "statement": "The following publicly available datasets were used in this study: TCGA: https://portal.gdc.cancer.gov/projects/TCGA-UVM; GEO: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22138.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33540700", "locator": "sections[26] \"Data Availability Statement\" paragraph 2", "quote": "The following publicly available datasets were used in this study: TCGA: https://portal.gdc.cancer.gov/projects/TCGA-UVM; GEO: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22138."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:33540700"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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The Prognostic Capacity of the Seven-Gene Signature", "row_count": 46, "column_count": 9}, "table": {"label": "Table 4", "caption": "Univariate analysis and multivariate analysis of the correlation of gene-signature risk score with outcomes among uveal melanoma patients in two cohorts.", "rows": [["Variable", "Univariate Cox Analysis", "Multivariate Cox Analysis"], ["Coef", "HR (95% CI)", "z", "p-Value", "Coef", "HR (95% CI)", "z", "p-Value"], ["TCGA-UVM (overall survival) *", "", "", "", "", "", "", "", ""], ["age", "0.0447", "1.05 (1.01–1.09)", "2.35", "0.0186", "0.101", "1.11 (0.976–1.25)", "1.57", "0.115"], ["gender (male vs. female)", "0.433", "1.54 (0.651–3.65)", "0.984", "0.325", "", "", "", ""], ["tumor stage (stage III vs. stage II)", "0.336", "1.4 (0.556–3.52)", "0.713", "0.476", "−3.06", "0.047 (0.00199–1.11)", "−1.9", "0.0579"], ["tumor stage (stage IV vs. stage II)", "4.37", "79.3 (7.55–834)", "3.64", "0.000269", "NA", "NA", "NA", "NA"], ["extrascleral extension (yes vs. no)", "1.54", "4.64 (1.5–14.4)", "2.66", "0.00774", "−4.25", "0.0142 (3.98× 10−13–5.1× 10 8)", "−0.343", "0.732"], ["tumor diameter", "0.155", "1.17 (1.01–1.35)", "2.12", "0.0344", "0.723", "2.06 (1.11–3.83)", "2.29", "0.0221"], ["tumor thickness", "0.111", "1.12 (0.949–1.32)", "1.33", "0.183", "", "", "", ""], ["radiation therapy (yes vs. no)", "1.68", "5.35 (1.09–26.3)", "2.07", "0.0389", "7.79", "2410 (4.34 × 10−8–1.33 × 10 14)", "0.617", "0.537"], ["ethnicity (hispanic or latino vs. not hispanic or latino)", "−16", "1.09 × 10−7 (0-Inf)", "−0.00205", "0.998", "", "", "", ""], ["tissue or organ of origin diagnosis (choroid vs. not choroid)", "−0.286", "0.751 (0.254–2.22)", "−0.517", "0.605", "", "", "", ""], ["mitotic count", "−0.0119", "0.988 (0.931–1.05)", "−0.394", "0.693", "", "", "", ""], ["chromosome 3 copy number", "−1.86", "0.156 (0.0574–0.422)", "−3.65", "0.00026", "2.76", "15.9 (0.894–281)", "1.88", "0.0597"], ["chromosome 6p copy number", "−1.06", "0.348 (0.176–0.687)", 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"capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE22138"], "resolved_accessions": ["GSE22138"], "statements": ["The following publicly available datasets were used in this study: TCGA: https://portal.gdc.cancer.gov/projects/TCGA-UVM; GEO: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE22138."], "basis": "The paper names GSE22138 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. 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